Explosive Blast Traumatic Brain Injury Geoffrey Ling, M.D., Ph.D.

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1 Explosive Blast Traumatic Brain Injury Geoffrey Ling, M.D., Ph.D. Colonel, Medical Corps, US Army Program Manager, DARPA Professor and Vice-Chair, Neurology, USUHS Director, Neuro Critical Care, WRAMC Associate Professor (adjunct), Anesthesiology & Critical Care Medicine, Johns Hopkins

2 TBI in Modern Warfare Traumatic brain injury remains a leading cause of death and disability Historically, head injury accounts for 15-20% of battle related casualties 50% of patients who died of wounds (DOW) Today, estimates of head injury is about 15% Carey, Milt Med 152: 6 (1987) Progmet et al, Milt Med 163: 482 (1998) Navy-Marine Combat Casualty Registry (2005) JTTR, Nov 2007

3 MORE THAN WE THINK? 25-40% OIF soldiers may y have suffered closed head injury Many (how many?) may have suffered more than one such injury Many (how many?) may have persistent subtle neurological symptoms (> 6 months) Estimates of 20-40% of exposed patients

4 Mechanisms of Traumatic Brain Injury Penetrating Injury Cause: Physical disruption of cells and fiber tracks, hemorrhaging, cell apoptosis Concussive Injury Cause: Mechanical loading leading to cell failure Hypoxia Cause: Lack of O 2 Explosive Blast Injury Cause: Mechanism of injury unknown

5 STATISTICS Unprecedented survival: 7.5 WIA:1.0 KIA IED blast related injuries significant source of casualty admissions Head Trauma - when compared to previous conflicts Increased # Hemicraniectomies Increased # Neurovascular Injury Increased # Complex Cranial-facial Injuries Newsweek, 2005 Armondo, WRAMC, 2006

6 Explosive Blast Injury - Categories Four categories of blast injury: Primary Caused by the direct blast energy Crush injuries, lacerations, hemorrhage common Secondary Caused by projectiles and other hazards created by the blast Rubble, building fragments, shrapnel, etc. Tertiary Inertial injuries caused by personnel being propelled by the blast (being thrown) Quaternary Inhalation, burns, and anything else not described by first three

7 Explosive Blast TBI Wide spectrum of neurological effects have been described Mild TBI Subtle cognitive deficits, neurobehavior changes, mood and affect issues Both can occur together Moderate TBI Loss of consciousness, overt structural damage Severe TBI Severe neurological deficits, subarachnoid hemorrhage, vascular changes (acute and chronic)

8 Mild Traumatic Brain Injury Traumatic brain injury symptoms Cognitive deficits Restlessness Behavioral affect Anxiety/increased stress levels Vertigo/loss of balance A growing number of U.S. troops whose body armor helped them survive bomb and rocket attacks are suffering brain damage as a result of the blasts The wound may come to characterize this war, much the way illnesses from Agent Orange typified the Vietnam War USA Today, 3 Feb, 2005 Thirty percent of U.S. troops surveyed have developed mental health problems three to four months after coming home from the Iraq war The survey of 1,000 troops found problems anxiety anger and an inability to concentrate, said Lt. Gen. Kevin Kiley Washington Post, 29 July, 2005 (Some are trying to make the case that these symptoms are mild TBI)

9 New TBI versus PTSD Mild Blast TBI Difficulty sleeping Emotional liability Difficulty concentrating Decreased appetite Other: May have post- concussive syndrome (headaches, etc) PTSD Sleep disturbance Outbursts of anger Difficulty concentrating Hypervigilance Exaggerated startle Other: Re-experience experience Avoidance DSM-IV

10 Severe Blast TBI Severe early cerebral edema Diffuse hyperemia Delayed vasospasm days after initial injury SAH

11 In adversity, there is opportunity Advances in Neurotrauma medical care Guideline directed pre-hospital TBI management Early decompressive hemicraniectomy Hypertonic brain resuscitation fluids Guideline directed in-hospital TBI management Appropriate use of vasopressors Transcranial Doppler at Echelon 3 Neurovascular diagnostics Endovascular intervention

12 What Happens to TBI Survivors? 14.3% (n=8574) of soldiers injured in Vietnam had moderate to severe TBI Of 160 of the surviving TBI patients following prospectively from Vietnam: 74% could live independently 59 % are active in their community Early evidence from OIF/OEF is a higher percentage of survivors from initial TBI with better functional outcome Sweeney and Smutok. Phys Therapy 1983; 63:2018.

13 What is the mechanism of injury? Returning to first principles

14 Present State of the Art Need to Know More Incomplete info about helmet performance Incomplete diagnosis No specific TBI treatments of any kind Currently, the assumption is injury results from blast overpressure Is this the complete story?

15 State of the Art Bowen-Richmond Curves Current metrics of blast injury are Binary: alive or dead Evaluate pessure damage to the lungs Do not address TBI Some unstudied characteristics of explosions: Rapid temperature change Environmental chemical composition changes Electromagnetic pulse Kinetic energy transfer

16 Paradox Many blast related TBI cases Few blast lung cases in isolation Few blast bowel cases

17 Rigorous Research Needed Evidence to provide basis for assumptions

18 What Elements of Explosions Can Cause TBI? Pressure Chemical Electromagnetic Kinetic? TBI Acoustic Light Thermodynamic Biological

19 PREventing Violent Explosion Neurological Trauma (PREVENT) A DARPA Program

20 Vision PREVENT Vision: Protecting soldiers from Traumatic Brain Injury through understanding the effects of explosive blast components Milestone: Identify physical mechanism (overpressure, EMP, etc.) and biological mechanism (apoptosis, etc.) of neurologic injury caused by explosion Metrics: Phase I (12 Mo.) Histology damage to cell axonal death and damage Epidemiology # of animals affected in standard environment and at different ranges Cognitive impairment Ability to perform cognitive tests Appetite Functional impairment Gait/movement Sleep patterns Two Phases Phase II (18 Mo.) Milestones: Refine Model Develop strategies, devices, and treatments to prevent injury from blast Metric: Prevention of injury as defined by achieving an injury severity score reduction of > 50%

21 PREVENT: 2 Arms Scientific Exploration (WRAIR Team) Explore injury mechanisms in Pig Tissue Epidemiological data Clinical Arm (Quantico Breacher Study) Unique cohort of Marines Repeated exposure to blasts at varying distance and magnitude Descriptive Model: (Phase 1 Deliverable) Determines causes of injury Improve operations (tactics and training) Improve mitigation (armor, helmet) Improve medicine (clinical and pharmacological treatment)

22 Pre-Clinical Pigs (Cumulative model) 8 animals per group Multiple distances, environments and explosive strengths Component model 12 animals per group Exposure to elements of blast sequentially in order to reproduce injury observed in cumulative model Epidemiological database Markers of injury Physiological Neurological Neurobehavioral Forensic information Used to supplement clinical markers FOUO FOUO Tissue study Blast bioreactor Allows for studies of molecular and cellular response in immediate acute phase Comprehensive Can be used testing as an exposure by experienced model for a specialists variety of forces Unique bioreactor designed by Dr. K. Parker (Harvard) Porcine experiments developed by seedling performer S. Parks (ORA, inc.) who originally demonstrated absence of blast injury from overpressure alone

23 Exposure Exposure testing will be carried out and monitored with the assistance of Special Forces Tests conducted at appropriate test sties Operationally relevant scenarios will guide placement of subjects and level of charge Sensors used have been proven to be rugged and robust in previous blast testing Thermal Plasma and ejecta effects: heat depositions in tissue may lead to protein denaturing Overpressure Peak overpressure Impulse Complex wave Electromagnetic band EMP Pulses exceeding levels where continuous fields have been shown to cause neurologic damage Radio frequencies Optical frequencies FOUO FOUO

24 Outcomes EEG Neurocognition Maze test Vasospasm Behavioral changes Feeding Sleep Neurologic Gait tested as a measure of motor function disruption Histopathology Cell counts across brain regions Comprehensive testing by experienced specialists Cognitive/Neurologic testing (WRAIR) Developed by investigator Histology and pathology of injury (WRAMC) Conducted by neurosurgeons with experience treating blast injured patients Collaborators include leading civilian TBI investigators FOUO FOUO

25 Unique Cohort Study Each Trainee exposed to: A) Pure Explosive Blast B) > 50 exposures over 2 week course C) Exposed to 20 grams 5 lbs TNT eq. D) Free field and enclosed environment Trainees report: Difficulty concentrating Mood changes Insomnia Proposed Study: 40 Subjects; 28 exposed to explosion, 12 not exposed Pre: Neurological testing, Cognitive testing, Neuroimaging, Mood/sleep diary 1 Week (Mid-course): Neurological testing, Cognitive testing 2 Week (Post-course): Neurological testing, Cognitive testing, Neuroimaging, review mood/sleep diary 3 Mo. (Post-course): Continue mood/sleep diary, neuroimaging and neurological and cognitive tests on available marines FOUO FOUO